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Definitive gene screen confirms MS suspects

22.09.2005

A cluster of genes on chromosome six is the only one that plays a significant role in multiple sclerosis (MS), according to the most complete genetic study to date in the disorder, presented at the 130th annual meeting of the American Neurological Association in San Diego.

"Our results confirm the strong role of the major histocompatibility complex genes in MS, and provides a definitive statement that no other region of the genome harbors a gene with a similar overall influence on MS genetics," said Jonathan Haines, Ph.D, of Vanderbilt University in Nashville, Tennessee, who presented on behalf of the International Multiple Sclerosis Genetics Consortium.

"A detailed examination of the major histocompatibility complex is critically important," said Haines, who suggests that this study may have profound implications for the future directions of MS genetics research.

The major histocompatibility complex (MHC) is a cluster of genes that play a critical role in the recognition of cells in the body as belonging to the body, i.e., not intruders such as bacteria or other pathogens.

When this system of recognition breaks down, the immune system may mistakenly launch an attack against cells, as happens in MS. Researchers believe that some genetic variations in MHC genes make people more susceptible to whatever environmental causes also contribute to MS.

Haines is one of the founders of an international team of researchers from many institutions that collected genetic data on 730 families with more than one case of MS from Australia, Scandinavia, the United Kingdom, and the United States.

Previous studies have implicated the MHC, but also regions on other chromosomes, as harboring genes that increase MS risk. Haines suggests that these studies failed to include enough subjects.

"This is the largest genetic linkage study on MS, and the first to be done using the latest technology, which provides very detailed coverage of the entire human genome," said Haines. "Other genes may still play an important role in MS, but finding them will require using new genomic techniques."

Multiple sclerosis is an enigmatic disease of the nervous system and results in the loss of myelin, a substance that normally insulates nerve fibers and speeds electrical conduction through the fibers. Patches of inflammation (known as plaques) occur throughout the brain and spinal cord resulting in the loss of myelin and sometimes the nerve fibers themselves.

Depending on which nerve fibers are hindered, patients can experience problems ranging from weakness and clumsiness to numbness, visual disturbances, and even emotional and intellectual alterations. In some patients, MS manifests itself in cycles of relapse and remission and patients may show little sign of the disease between attacks.

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